PMN function is modulated by ligand binding to surface receptors, which induces transient increases in cytosolic Ca2+ mobilizes protein kinase C (PKC), and initiates PMN activation. Ca2+ signalling is altered by polyamines, which are prevalent in gingival fluid at inflamed periodontal sites. We hypothesize that polyamines significantly enhance Ca2+ mobilization in PMN and thereby modulate many essential responses to extracellular stimuli. We will test this hypothesis in vitro by examining the effects of polyamines at three levels of action: 1) Modulation of chemoattractant-induced Ca2+ mobilization, 2) Modulation of PKC translocation and phosphorylation of cell proteins, and 3) Modulation of PMN functions regulated by Ca2+ and PKC. These studies will provide a better understanding of the complex mechanisms involved in local modulation of PMN function in periodontal disease and other inflammatory disorders.